Search Results (328)

Electronic waste (e-waste) recycling releases heavy metals into surrounding environments, creating potential health risks for nearby populations, particularly pregnant women and developing fetuses. This systematic review evaluated human evidence linking prenatal exposure to heavy metals originating from informal e-waste recycling with adverse pregnancy and neonatal outcomes. Electronic databases, including PubMed and Scopus, were searched through 23 September 2025, for studies measuring heavy metal exposure among pregnant women or neonates living in e-waste–affected communities. Following the Navigation Guide methodology, eight observational studies met the inclusion criteria and were assessed for risk of bias and strength of evidence. Across studies, concentrations of heavy metals were higher in exposed populations and were detected in maternal blood, placenta, cord blood, urine, and meconium samples from exposed populations. Prenatal exposure was consistently associated with adverse outcomes, with many studies reporting statistically significant associations between heavy metal exposure and reduced birth weight, length, head circumference, gestational age, neonatal body mass index, lower Apgar scores, impaired neonatal neurobehavioral development, placental molecular alterations, endocrine disruption, and increased neonatal DNA damage. Overall, the evidence was rated as moderate quality with sufficient evidence linking prenatal heavy-metal exposure from e-waste to impaired fetal growth and neonatal development, and limited evidence for pregnancy complications. These findings highlight the need for improved regulation of e-waste recycling and strengthened public health protections for vulnerable populations. Full article

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy has raised concerns regarding possible fetal consequences, including potential effects on auditory system development. Although the current literature suggests that overt congenital hearing loss is uncommon among newborns exposed in utero, subtle cochlear functional alterations may not be detectable through conventional threshold-based screening alone. The objective of this study is to investigate whether in utero exposure to maternal COVID-19 is associated with early cochlear functional changes in newborns, as assessed by frequency-specific transient evoked otoacoustic emission (TEOAE) amplitude ratios, and to determine whether such alterations are accompanied by differences in click-evoked auditory brainstem response (ABR) thresholds. Materials and Methods: This prospective cohort study was conducted between October 2021 and September 2022 and included 61 pregnant women: 30 with laboratory-confirmed SARS-CoV-2 infection during pregnancy (study group) and 31 without documented infection (control group). All newborns underwent standardized audiological evaluation shortly after birth, including otoscopy, TEOAE, click-evoked ABR, and tympanometry. Frequency-specific TEOAE amplitude ratios at 500, 1000, 1500, 2000, and 4000 Hz were compared between groups. A logistic regression analysis was performed to identify audiological predictors of newborn exposure to SARS-CoV-2 in utero. Results: No significant differences were observed in ABR thresholds or in TEOAE “pass/refer” outcomes between the control and study groups, indicating the absence of clinically overt HL. However, newborns exposed to SARS-CoV-2 in utero showed significantly reduced TEOAE amplitude ratios at 2000 Hz (p = 0.0077) and 4000 Hz (p = 0.020). Logistic regression identified the 4000 Hz amplitude ratio as an independent negative predictor of in utero exposure (OR = 0.75; p = 0.0352). No significant differences were detected at lower frequencies. Conclusions: Maternal COVID-19 during pregnancy was not associated with immediate neonatal HL but was linked to subtle high-frequency cochlear functional modulation. Longitudinal audiological follow-up is needed to clarify the clinical significance of these findings. Full article

Background: The incidence of early-onset colorectal cancer (EOCRC) is rising globally, yet its underlying risk factors remain incompletely understood, particularly in cases without recognised hereditary syndromes. Objectives: To update and synthesise the current body of evidence on modifiable and non-modifiable risk factors for sporadic early-onset colorectal cancer. Methods: A systematic review of peer-reviewed articles published in English reporting original observational research examining risk factors for sporadic early-onset colorectal cancer (<50 years old) was conducted. PubMed and EMBASE databases were searched from inception to March 2025. Across studies, effect measures varied; therefore, the synthesis focused on the consistency of associations rather than the direct comparison of effect sizes. Results: The initial search identified 2575 papers; 34 studies were included after screening. Several consistent associations were identified, with dietary and lifestyle factors along with metabolic conditions emerging as key risk factors. EOCRC risk was higher in males (adjusted odds ratio (aOR) 1.36–2.21 across studies), individuals of Caucasian ethnicity (aORs 1.48–2.56), and in individuals whose age was approaching 50 years (per year, aORs 1.05–1.11). Putatively sporadic EOCRC was associated with a family history of CRC or other cancers (aORs up to 8.61). Other key factors linked to higher risk included obesity (aORs 1.92–2.88; adjusted Hazard Ratios (aHRs) 1.04–1.82), metabolic syndrome (aORs 1.25–2.48; aHRs 1.2–1.26), diabetes (aORs 1.24–3.42), Western dietary patterns (aORs 1.84–2.99), and sedentary behaviours (adjusted relative risks (aRR) 1.69–2.44). Moderate-to-vigorous exercise appeared protective (aORs 0.34–0.58), as did higher vitamin D levels (aHRs 0.41–0.61). Evidence for smoking, alcohol, medications and early/in utero environmental exposures was inconsistent. Conclusions: Lifestyle and metabolic factors, including Western dietary patterns, obesity and sedentary behaviours, were associated with sporadic EOCRC. Family history also emerged as a significant contributor to putatively sporadic disease, suggesting heritable influences beyond recognised syndromes and interplay between environmental factors and genetic predisposition. Future research should focus on integrated tumour and germline profiling, including broader genomic analyses in well-characterised cohorts, to better understand potential pathogenic mechanisms and support the development of risk stratification approaches. Full article

Objective: Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been associated with altered neonatal adaptation, but its relationship with early elimination patterns remains unclear. Given the role of serotonin in gastrointestinal and urinary physiology, we aimed to evaluate the association between maternal SSRI use during pregnancy and time to first stool and time to first void in healthy neonates. Methods: In this retrospective matched cohort study, neonates exposed to SSRIs in utero were matched 1:1 with unexposed controls by gestational age (GA) and weight-for-gestational-age category. The primary outcomes were time to first void and time to first stool. Multivariable linear regression was performed using log10-transformed time to first stool, adjusting for maternal age, GA, and neonatal sex. Sensitivity analyses included size-for-gestational-age and time to first feeding. Results: A total of 266 neonates were included (133 SSRI-exposed, 133 unexposed). Time to first stool was shorter in SSRI-exposed neonates compared with unexposed neonates (median 7.4 vs. 8.6 h, p = 0.023), while the time to first void did not differ. In adjusted analysis, SSRI exposure remained associated with shorter time to first stool (β = −0.08, 95% CI −0.16 to −0.001, p = 0.035), corresponding to an approximate 17% reduction. The association was consistent across sensitivity analyses. Meconium-stained amniotic fluid was associated with shorter time to first stool among SSRI-exposed neonates but not in unexposed neonates. The overall model explained a limited proportion of variance. Conclusions Prenatal SSRI exposure was associated with modest but consistent reduction in time to first stool, without affecting time to first void. While the clinical significance remains uncertain, these findings suggest a potential influence of in utero SSRI exposure on early neonatal gastrointestinal adaptation, which may be influenced by intrapartum conditions. Full article

Background: Microplastics (MPs) have rapidly emerged as pervasive environmental contaminants with growing implications for human health. Evidence now shows that MP exposure may begin during pregnancy and extend into infancy. Foetal exposure to MP raises questions about MP presence within reproductive organs, maternal–foetal MP transfer and the potential impact of MP on women’s reproductive health. Objectives: To synthesise current evidence on the presence and distribution of microplastics in the female reproductive system and pregnancy-related organs. Methods: A systematic review of literature was conducted using Embase and Medline databases, supplemented by reference screening and manual searches. Studies were eligible if they examined MP in human female reproductive organs or pregnancy-related tissues and were published in English. Results: Eleven studies met the inclusion criteria. Across studies, MP detection varied substantially due to differences in sampling protocols, analytical techniques, and particle size detection thresholds. Cross-contamination and analytical method variability remained major methodological concerns. MP were consistently identified in follicular fluid, placental tissue, amniotic fluid, cord blood, and meconium. Conclusions: The presence of MP in both maternal and foetal compartments supports the possibility of in utero maternal-foetal MP transfer. A standardised protocol should be used to assess MP presence and MP’s impact on organs and tissues. The current variability of diagnostic tests, the lack of cofounding variables control and the reduced sample sizes limit the ability to determine how clinically relevant MP exposure is during pregnancy and to women’s reproductive health. Full article

Volatile organic compounds (VOCs) are ubiquitous pollutants, and exposure from in utero through childhood may impair neurodevelopment. However, compound-specific risks remain unclear. This systematic review and meta-analysis examined associations between VOC exposure and child neurodevelopmental outcomes. A systematic search of PubMed, Scopus, and Embase was conducted until August 2025, yielding 1213 records. Quality assessment was performed using the Newcastle–Ottawa Scale and risk of bias using the ROBINS-E tool. Pooled odds ratios (ORs) were calculated using random-effects models, with heterogeneity evaluated via I² statistics. Subgroup analyses explored for study design, exposure timing, and country income level. Twenty-eight studies were included in the final analysis. Of the 18 VOCs analyzed, five compounds, propionaldehyde (pooled OR = 1.84; 95% CI 1.19–2.49), styrene (pooled OR = 1.69; 95% CI 1.30–2.21), vinyl chloride (pooled OR = 1.53; 95% CI 1.24–1.89), acrolein (pooled OR = 1.48; 95% CI 1.08–2.04), and trichloroethylene (OR = 1.21; 95% CI 1.04–1.41), demonstrated statistically significant adverse associations with neurodevelopment. Benzene showed borderline significance. Heterogeneity ranged from 0–47%. Subgroup analyses identified significant effect modification for 1,3-butadiene by study design and exposure timing and higher pooled estimates for ethylbenzene in high-income countries. Full article

Maternal nutrition during pregnancy critically influences fetal programming, shaping the offspring’s lifelong health and disease susceptibility. Both undernutrition and overnutrition affect fetal metabolism, predisposing offspring to obesity and cardiometabolic disorders in adulthood. This review examines current evidence on how maternal nutrition, particularly overnutrition and its complications, such as gestational diabetes mellitus (GDM) and obesity, affects offspring health. It also explores the biochemical and epigenetic mechanisms underlying aberrant fetal programming induced by an unfavorable intrauterine environment. Excess nutrient exposure in utero alters fetal metabolic pathways by modifying the expression of key metabolic genes and nutrient sensors, increasing susceptibility to metabolic syndrome later in life. Maternal obesity has additionally been linked to cognitive dysfunction, immune alterations, and elevated cancer-related mortality in the offspring. GDM exposure disrupts fetal hypothalamic development, impairing appetite regulation. Emerging evidence suggests that epigenetic changes induced by maternal overnutrition may be transmitted across generations and that paternal obesity may also contribute to fetal metabolic programming. Although lifestyle interventions during pregnancy have been tested, they show limited long-term benefits, whereas pre-pregnancy BMI remains the strongest predictor of offspring obesity, emphasizing the critical role of preconception care and the prevention of overweight in women of reproductive age. Full article

Background: n-3 PUFA derived from marine sources, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exhibit potential for breast cancer prevention. In contrast, higher dietary intakes of n-6 PUFA, such as linoleic acid (LA), have been implicated in promoting mammary tumourigenesis. However, there is a need for further exploration into how n-3 PUFA influence breast cancer development in comparison to different amounts and sources of LA. Objective: The purpose of this study was to compare the effects of n-3 PUFA-enriched diets versus n-6 PUFA diets differing in LA content, including corn oil (50% LA) and safflower oil (70% LA), on mammary tumour development in a HER2+ breast cancer model. Methods: Using the HER2+ breast cancer MMTV-neu(ndl)YD5 transgenic mouse model, this study determined the effects of: (1) 10% w/w corn oil (CO, n-6 PUFA, n = 14), (2) 10% w/w safflower oil (SO, n-6 PUFA, n = 14), (3) 3% w/w menhaden oil + 7% w/w CO (3% FO 7% CO, n-3 PUFA, n = 12), and (4) 3% w/w menhaden oil + 7% w/w SO (3% FO 7% SO, n-3 PUFA, n = 14) on puberty onset, tumour incidence, tumour volume, and tumour number in utero until 20 weeks of age. Results: Mice fed the n-3 PUFA-enriched diets showed a lower trajectory of tumour development compared to the n-6 PUFA diets, although the differences for palpated tumour volume and number over time reached significance only between the 10% CO and 3% FO 7% CO groups. This suggests that high LA content in CO may represent a threshold for promoting tumour growth whereby further LA content marginally influences additional tumour development. Exposure to the CO n-6 PUFA diet further resulted in earlier onset of puberty compared to the n-3 PUFA-enriched diet containing CO. To investigate the underlying mechanisms, a qPCR analysis of mammary glands and tumour tissue revealed that the n-3 PUFA diets downregulated the expression of pro-tumourigenic immune markers, including CD206 and F4/80 in the mammary glands and the cannabinoid receptor CB2 in tumours, compared to the n-6 PUFA diets. Conclusions: These findings indicate that the presence of dietary n-3 PUFA plays a key role in modulating mammary tumour development, which may be further influenced by the underlying n-6 PUFA background. The associated changes in immune markers suggest that n-3 PUFA exert anticancer effects in part by shifting the tumour immune microenvironment toward an anti-tumour phenotype and modulating cannabinoid receptor signalling. Collectively, this work informs future human studies investigating the role of dietary fat composition in breast cancer risk. Full article

Background: The effect of intrauterine exposure to SARS-CoV-2 infection during pregnancy on neurodevelopment and growth trajectories during the first year of life remains under investigation. Methods: We retrospectively reviewed the electronic medical records of all pregnant women who received care at Mayo Health System and tested positive for SARS-CoV-2 (RT-PCR) from March 2020 through October 2021 and examined the effects of fetal sex and trimester of maternal SARS-CoV-2 infection on the risk of neurodevelopmental disorder diagnosis and growth trajectories of head circumference (HC) and body weight (BW) percentiles over the first year of life using linear mixed models. Results: We observed that a higher percentage of male infants (n = 357), compared to females (n = 344), have neurodevelopmental disorders (10.9% vs. 5.2%, p = 0.008), and infants exposed to maternal SARS-CoV-2 infection in the second (n = 183) or third trimester (n = 358) have a higher prevalence of neurological diagnoses compared to those exposed in the first trimester (n = 160) (1st vs. 2nd vs. 3rd trimester: 0% vs. 0.9% vs. 0.7%, respectively, p = 0.037). In addition, female infants, compared to males, had significantly lower BW (B = −0.04, p < 0.0001) and HC (B = −0.06, p < 0.0001) percentile growth trajectories over the first year of life. Moreover, infants exposed to maternal SARS-CoV-2 infection in the second trimester had a significantly lower BW percentile growth trajectory (B = −0.01, p = 0.006), while infants exposed to maternal SARS-CoV-2 infection in the third trimester had a significantly lower HC percentile growth trajectory (B = −0.02, p = 0.02). Conclusions: In utero exposure to maternal SARS-CoV-2 infection could have long-term effects on growth trajectories, depending on the infant’s sex and timing of exposure. Full article

Background and Objectives: Antiretroviral therapy used during pregnancy in HIV infected women effectively reduces vertical transmission, though concerns about potential adverse newborn outcomes persists. This study focused on prematurity and low birth weight in antiretroviral HIV-exposed children in two major Romanian centers, Bucharest and Constanța, in the context of free access to antiretroviral treatment for pregnant women in Romania since 2001. Materials and Methods: A retrospective observational study was performed including couples of HIV-infected women and their live singleton newborns from 2006 and 2012. Preterm delivery was defined as birth before week 37 and low birth weight was defined as birth weight less than 2500 g in full-term babies. Results: A total number of 352 children and 313 women were enrolled. Mean maternal age at delivery was 23.1 years. Mean newborn birth weight was 2726 g. In the children group, 191 (54.2%) were boys, and the rate of HIV transmission was 13.9%. The prematurity rate was 21.5% and low birth weight rate was 25.56%. Preterm birth was associated with high HIV RNA in the third trimester, HIV-positive final status in infants, and vaginal delivery. Low birth weight was associated with lack of antiretroviral treatment during pregnancy and HIV-positive status in infants. No association was found between prematurity and low birth weight in full-term newborns and exposure to any antiretroviral class, any specific antiviral drug, or with any number of maternal regimens, duration of antiretroviral treatment prior to conception, or maternal exposure during puberty. Conclusions: In our study, preterm birth was significantly associated with HIV vertical transmission in newborns and with exposure to high maternal viral replication during the last trimester of pregnancy. Low birth weight in full-term babies was significantly associated with lack of antiretroviral exposure in utero in our analysis. Full article

Background/Objectives: The renin–angiotensin–aldosterone system (RAAS) is pivotal for neonatal circulation and renal adaptation; however, postnatal changes in serum renin and aldosterone immediately after birth remain unclear. This study aimed to establish postnatal changes in these hormones at birth and over the first week of life. Methods: We retrospectively analyzed 374 neonates admitted to Kobe University Hospital between October 2020 and September 2023, with serum renin and aldosterone measured on days 0 and 5 of life. Exclusion criteria were multiple congenital anomalies, severe asphyxia, major peripartum hemorrhage, and in utero exposure to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Hormone levels were compared between term and preterm infants, and correlations with gestational age were assessed. Results: Serum renin concentrations were higher on day 0 than on day 5 (median 99.9 pg/mL [2.6–773.3] vs. 19.9 pg/mL [0.6–2304], p < 0.0001), and aldosterone concentrations similarly decreased (714 pg/mL [6.9–6334] vs. 551 pg/mL [0–11,930], p < 0.0001). At birth, renin and aldosterone levels did not differ significantly between groups. By day 5, both renin (32.8 pg/mL [0.6–2304] vs. 14.5 pg/mL [0.6–208]) and aldosterone (689 pg/mL [4–11,930] vs. 471 pg/mL [13–4697]) concentrations were significantly higher in preterm than in term neonates (p < 0.0001). Conclusions: This study describes early postnatal changes in renin and aldosterone, with higher concentrations at birth than on day 5 and persistently elevated levels in preterm infants. These findings indicate increased RAAS activity in preterm neonates and suggest a greater vulnerability to fluid, electrolyte, and blood pressure instability during early life. Full article

Introduction: We previously showed that baboon offspring born to mothers deprived of estrogen during the second half of gestation exhibited insulin resistance prior to and after the onset of puberty. Moreover, the size of skeletal muscle myofibers and the number of microvessels important for delivery of insulin/glucose to myofibers were lower in near-term fetuses deprived of estrogen during pregnancy, and myofiber capillarization remained reduced in post-pubertal offspring deprived of estrogen in utero. However, it remains to be determined whether skeletal muscle size is restored to normal in animals deprived of estrogen in utero after the onset of puberty/gonadal estrogen production. Methods: To answer this question, the current study quantified the size and number of slow and fast fibers in biopsies of vastus lateralis skeletal muscle obtained from post-pubertal female baboon offspring 9–12 years old, born to mothers who were untreated (n = 7) or treated during the second half of gestation with letrozole (n = 6; suppressed maternal and fetal estrogen by >90%) or letrozole plus estradiol benzoate (n = 3). Results: Results indicated that skeletal muscle slow and fast fiber growth in female offspring appeared to occur by hypertrophy and that respective size of fibers after the onset of puberty was similar in offspring born to mothers who were untreated or deprived of estrogen in utero. Conclusions: Postnatal myofiber hypertrophy likely reflects the impact of the pubertal surge in and continued exposure of offspring myofibers to ovarian estrogen and is restored to normal in post-pubertal female offspring deprived of estrogen in utero. Full article

White-matter development during fetal life represents one of the most vulnerable processes to environmental disruption, as it relies on the precisely timed proliferation, migration, and differentiation of oligodendrocyte lineage cells. Among environmental threats, exposure to toxic compounds contained in tobacco smoke and vaping aerosols represents a major yet preventable risk during pregnancy. Despite growing awareness, tobacco smoking remains widespread, and a substantial proportion of the population—including pregnant women—continues to perceive electronic nicotine delivery systems (ENDS) as less harmful, a misconception that contributes to persistent prenatal exposure. These products expose the fetus to numerous substances that readily cross the placenta and reach the developing brain, including compounds with endocrine-disrupting activity, where they interfere with white-matter development. Epidemiological and neuroimaging studies consistently reveal microstructural alterations in white matter that correlate with long-term cognitive and behavioral impairments in offspring exposed in utero. These alterations may arise from both nicotine-specific pathways and the actions of other toxicants in cigarette smoke and ENDS aerosols that cross the placenta and disrupt white-matter emergence and maturation. Preclinical research provides mechanistic insight: nicotine acts directly on nicotinic acetylcholine receptors (nAChRs) in oligodendrocyte precursor cells, disrupting calcium signaling and differentiation, while additional constituents of smoke and vaping aerosols also affect astrocyte and microglial function and disturb the extracellular milieu required for proper myelination. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder in both children and adults. Pediatric MASLD, however, is not simply an early form of adult disease, as it exhibits distinct developmental, histological, and metabolic features. Emerging evidence suggests that these characteristics arise from a complex, multi-hit continuum that begins in utero. Maternal obesity, gestational diabetes, and poor diet quality during pregnancy have been associated with greater hepatic steatosis in offspring, raising the possibility that intrauterine exposure to dyslipidemia, hyperglycemia, and elevated free fatty acid flux may contribute to early hepatic lipid deposition. After birth, feeding behaviors such as a prolonged breastfeeding appear protective, whereas formula feeding, especially high added-sugar formulations, may accelerate rapid weight gain and increase susceptibility to later steatosis. Early childhood diets high in added sugars, saturated fats, and ultra-processed foods may further promote hepatic lipogenesis and inflammation and interact with underlying genetic susceptibility. Given the heterogeneity of available human cohort studies and mechanistic model systems, this narrative review summarizes converging evidence from prenatal, postnatal, and early childhood nutritional exposures and their relationship to offspring hepatic lipid accumulation, emphasizing early-life windows for intervention to reduce the burden of pediatric MASLD. Full article

Background/Objectives: Children with perinatal HIV (PHIV) are more at risk for hearing loss than HIV-unexposed (HU) children. Due to medical advances maternal HIV transmission to newborns is decreasing, but in children with perinatal HIV exposure, uninfected (PHEU) is increasing. The objectives were to evaluate (1) pure-tone audiometry and cochlear and auditory neural function in children with perinatally acquired HIV (PHIV), children with perinatal HIV exposure but uninfected (PHEU), and HIV-unexposed (HU) children and (2) differences in hearing measures for children with PHIV according to HIV disease severity. Methods: Three hundred and thirty-three children (105 PHIV [58 girls, 47 boys], 101 PHEU [51 girls, 50 boys], and 127 HU [65 girls, 62 boys]), aged 11–14 years, completed a hearing assessment that included a hearing-related questionnaire, otoscopy, tympanometry, pure-tone thresholds, distortion product otoacoustic emissions (DPOAEs) for cochlear function, and auditory brainstem responses (ABRs) for neural function. Results: Pure-tone thresholds, DPOAE, and ABR measures were similar in the three groups. Children with PHIV had a higher prevalence of hearing loss compared to children with PHEU and HU children. Children with PHIV and greater historical HIV disease severity had similar hearing, DPOAEs, and ABRs to those with lesser HIV disease severity. Conclusions: In utero HIV acquisition or HIV exposure might not affect the cochlear and neural function up to the level of the brainstem. Children with PHIV had a higher prevalence of hearing loss; it is possible there is a difference in central auditory processing across the three groups of children. Hearing loss identification is important since it may impact social and educational development. Full article